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Updated: Jun 5, 2025
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Published on: March 28, 2025
Plasma proteomics for novel biomarker discovery in childhood tuberculosis
Andrea Fossati1,2,3, Peter Wambi4, Devan Jaganath5,6
1J. David Gladstone Institutes, San Francisco, 94158, California,USA.
Insights
Researchers developed a novel plasma biosignature to improve tuberculosis (TB) diagnosis in children. This non-sputum biomarker accurately identifies pediatric TB, potentially speeding up treatment and saving lives.
Area of Science:
- Biomarker discovery
- Proteomics
- Pediatric infectious diseases
Background:
- Tuberculosis (TB) remains a leading cause of child mortality globally.
- Current diagnostic methods for pediatric TB are often inaccurate and invasive.
- There is a critical need for non-sputum-based biomarkers for early TB detection in children.
Purpose of the Study:
- To develop a plasma-based biosignature for diagnosing tuberculosis in children.
- To identify novel protein biomarkers indicative of pediatric TB.
- To improve the accuracy and speed of pediatric TB diagnosis.
Main Methods:
- Utilized high-throughput data-independent acquisition mass-spectrometry (DIA-PASEF-MS) on plasma samples from 511 children.
- Analyzed proteomic data from children with confirmed TB and those with non-TB respiratory illnesses.
- Employed machine learning to derive predictive biosignatures.
Main Results:
- Identified 47 differentially regulated proteins between TB and non-TB pediatric groups.
- Developed three parsimonious biosignatures (4-6 proteins) with high diagnostic accuracy (AUC 0.86-0.88).
- Biosignatures met or exceeded WHO target product profile thresholds for TB screening tests.
Conclusions:
- A novel, non-sputum plasma biosignature for pediatric TB diagnosis has been developed.
- This biosignature shows potential to significantly reduce diagnostic delays in children.
- The findings offer insights into host response in pediatric TB and a tool for global disease management.
Abstract:
Failure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, and identifying novel non-sputum-based TB biomarkers to improve pediatric TB diagnosis is a global priority. We sought to develop a plasma biosignature for TB by probing the plasma proteome of 511 children stratified by TB diagnostic classification and HIV status from sites in four low- and middle-income countries, using high-throughput data-independent acquisition mass-spectrometry (DIA-PASEF-MS). We identified 47 proteins differentially regulated (BH adjusted p-values < 1%) between children with microbiologically confirmed TB and children with non-TB respiratory diseases (Unlikely TB). We further employed machine learning to derive three parsimonious biosignatures encompassing 4, 5, or 6 proteins that achieved AUCs of 0.86-0.88 all of which exceeded the minimum WHO target product profile accuracy thresholds for a TB screening test (70% specificity at 90% sensitivity, PPV 0.65-0.74, NPV 0.92-0.95). This work provides insights into the unique host response in pediatric TB disease, as well as a non-sputum biosignature that could reduce delays in TB diagnosis and improve detection and management of TB in children worldwide.
